Altered cognitive function is a common and distressing experience reported by individuals with cancer. Cognitive dysfunction can be devastating, impairing an individual's ability to cope with a cancer diagnosis and make treatment decisions, work, and attain personal goals. Immune system responses to malignant cells and tissue injury are likely to be a factor contributing to alterations in cognition. Specifically, pro-inflammatory cytokines can induce symptoms and behavioral responses, called 'sickness behavior', that generally favor the recovery of the individual but can be detrimental if excessive. Cognitive changes are known to occur alongside these sickness behavior responses and may be a component of cytokine-induced responses to the cancer and it's treatment. Little research has examined the relationship between cognitive and immune function in individuals with cancer or whether alterations in attention and memory are sickness behavior responses. The specific aims of this project are 1) to examine if a relationship exists between deficits in attention and memory and alterations in the expression of pro-inflammatory cytokines and selected biomarkers of inflammation in individuals newly diagnosed with colorectal cancer (CRC) prior to any treatment, and 2) to determine whether sickness behavior responses are associated with impaired cognitive function in individuals newly diagnosed with CRC. The project uses a descriptive comparative design with a sample of 50 individuals newly diagnosed with CRC and a comparison group of 50 individuals without CRC having a negative screening colonoscopy. Objective measures of attention and memory;serum levels of pro-inflammatory cytokines and selected biomarkers of inflammation;subjective measures of immune-related sickness behavior, and measures of possible covariates will be obtained at one time point prior to any treatment for colorectal CRC or within 12 months of a negative screening colonoscopy. Correlation and multiple linear regression analyses will be used to 1) examine the relationships between cognitive function and pro-inflammatory cytokines and selected biomarkers of inflammation in individuals with and without CRC, and 2) assess the relationship between sickness behavior responses and impaired cognitive function in individuals with CRC. This study will provide new information about the role of the immune response in alterations in cognitive function in cancer and will allow for the development of interventions that support optimal cognitive functioning. The broad, long-term objectives of this research are to contribute to the knowledge base of 1) altered cognitive function and immune responses in CRC survivors during the initial phase of the illness, and 2) potential mechanisms that may underlie cognitive alterations in individuals with cancer. This project addresses the NINR's research emphasis of managing symptoms and delineating causative mechanisms underlying symptoms. Further, this project addresses NINR's strategy for advancing science through the integration of biological and behavioral sciences. PUBLIC HEALTH RELEVANCE: Colorectal cancer affects approximately 150,000 individuals yearly in the United States and is characterized by an over expression of pro-inflammatory cytokines. These pro-inflammatory cytokines are produced as part of the immune system's response to the presence of cancer cells and can alter cognitive function and an individual's ability to function at home, work, and in society. Information from this study will be used to develop interventions to support cognitive function in individuals with colorectal cancer.